STARD4 StAR related lipid transfer domain containing 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: STARD4provided by HGNC
Official Full Name: StAR related lipid transfer domain containing 4provided by HGNC
Primary source: HGNC:HGNC:18058
See related: Ensembl:ENSG00000164211 MIM:607049; AllianceGenome:HGNC:18058
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: Cholesterol homeostasis is regulated, at least in part, by sterol regulatory element (SRE)-binding proteins (e.g., SREBP1; MIM 184756) and by liver X receptors (e.g., LXRA; MIM 602423). Upon sterol depletion, LXRs are inactive and SREBPs are cleaved, after which they bind promoter SREs and activate genes involved in cholesterol biosynthesis and uptake. Sterol transport is mediated by vesicles or by soluble protein carriers, such as steroidogenic acute regulatory protein (STAR; MIM 600617). STAR is homologous to a family of proteins containing a 200- to 210-amino acid STAR-related lipid transfer (START) domain, including STARD4 (Soccio et al., 2002 [PubMed 12011452]).[supplied by OMIM, Mar 2008]
Expression: Ubiquitous expression in duodenum (RPKM 9.8), small intestine (RPKM 9.3) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q22.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (111496033..111512535, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (112006333..112022835, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (110831731..110848233, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential regulation of STARD1, STARD4 and STARD6 in the human ovary.
Title: Differential regulation of STARD1, STARD4 and STARD6 in the human ovary.
Membrane specificity of the human cholesterol transfer protein STARD4.
Title: Membrane specificity of the human cholesterol transfer protein STARD4.
SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.
Title: SREBF2-STARD4 axis confers sorafenib resistance in hepatocellular carcinoma by regulating mitochondrial cholesterol homeostasis.
[Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism].
Title: [Steroidogenic acute regulatory protein-related lipid transfer 4 (StarD4) promotes breast cancer cell proliferation and its mechanism].
STARD4 promotes breast cancer cell malignancy.
Title: STARD4 promotes breast cancer cell malignancy.
STARD4 has a conserved alpha-helix/beta-grip fold with a deep hydrophobic pocket.STARD4 binds sterol in the pocket and transport sterol between liposomes. Sterol binding requires a conformational change to form a complementary pocket.
Title: Structural analysis of human sterol transfer protein STARD4.
Knockdown of STARD4, a sterol transporter, leads to large changes in the lipidome. STARD4-KD cells also have large changes in their mRNA profile. There is an increase in cellular cholesterol, including in late endosomes. These results indicate that STARD4 plays important roles in lipid homeostasis.
Title: Stable reduction of STARD4 alters cholesterol regulation and lipid homeostasis.
This study shows that nonvesicular sterol transport mechanisms and STARD4 in particular account for a large fraction of sterol transport between the plasma membrane and the ERC.
Title: Role of STARD4 in sterol transport between the endocytic recycling compartment and the plasma membrane.
Studies show the 3 steroidogenic acute regulatory-related lipid transfer (START) domain proteins StarD4, StarD5 and StarD6 have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization.
Title: The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism.
The data indicate a role for STARD4 in nonvesicular transport of cholesterol from the plasma membrane and the endocytic recycling compartment to the endoplasmic reticulum and perhaps other intracellular compartments as well.
Title: STARD4 knockdown in HepG2 cells disrupts cholesterol trafficking associated with the plasma membrane, ER, and ERC.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH103232 (e-PCR)
- UniSTS:97564

RH103311 (e-PCR)
- UniSTS:97642

SHGC-67307 (e-PCR)
- UniSTS:89991

STARD4__5333 (e-PCR)
- UniSTS:464571

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cholesterol binding	IBA Inferred from Biological aspect of Ancestor more info
enables cholesterol binding	IDA Inferred from Direct Assay more info	PubMed
enables cholesterol transfer activity	IBA Inferred from Biological aspect of Ancestor more info
enables cholesterol transfer activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cholesterol import	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol import	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol transport involved in cholesterol storage	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol transport involved in cholesterol storage	IDA Inferred from Direct Assay more info	PubMed
involved_in intracellular cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular cholesterol transport	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of bile acid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cholesterol metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: stAR-related lipid transfer protein 4

Names: START domain containing 4, sterol regulated; START domain-containing protein 4; StAR-related lipid transfer (START) domain containing 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001308056.2 → NP_001294985.1 stAR-related lipid transfer protein 4 isoform a

See identical proteins and their annotated locations for NP_001294985.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode isoform a.

Source sequence(s)

AK026207, AK054566, AK125317, AL710253, BI091150, BU607573, DB475661

Consensus CDS

CCDS4104.1

UniProtKB/Swiss-Prot

Q86TN9, Q96DR4

UniProtKB/TrEMBL

A8K2P7

Related

ENSP00000427478.2, ENST00000505803.5

Conserved Domains (1) summary

cl14643
Location:5 → 205

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_001308057.2 → NP_001294986.1 stAR-related lipid transfer protein 4 isoform b

See identical proteins and their annotated locations for NP_001294986.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) contains alternate 3' exon structure, resulting in an alternate 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a distinct C-terminus and is shorter than isoform a. Both variants 3 and 4 encode isoform b.

Source sequence(s)

AK308851, BC042956

Consensus CDS

CCDS78046.1

UniProtKB/Swiss-Prot

Q96DR4

Related

ENSP00000427639.1, ENST00000502322.5

Conserved Domains (1) summary

cl14643
Location:5 → 137

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_001308058.2 → NP_001294987.1 stAR-related lipid transfer protein 4 isoform b

See identical proteins and their annotated locations for NP_001294987.1

Status: VALIDATED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and contains alternate 3' exon structure, resulting in an alternate 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (b) has a distinct C-terminus and is shorter than isoform a. Both variants 3 and 4 encode isoform b.

Source sequence(s)

AK308851, BC042956, DB475661, DT220890

Consensus CDS

CCDS78046.1

UniProtKB/Swiss-Prot

Q96DR4

Conserved Domains (1) summary

cl14643
Location:5 → 137

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_001308059.2 → NP_001294988.1 stAR-related lipid transfer protein 4 isoform c

See identical proteins and their annotated locations for NP_001294988.1

Status: VALIDATED

Description

Transcript Variant: This variant (5) contains an additional exon, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a. Both variants 5 and 6 encode isoform c.

Source sequence(s)

AK026207, AK054566, AK125317, BI091150, BP234859, BU607573, DB475661

UniProtKB/Swiss-Prot

Q96DR4

Conserved Domains (1) summary

cl14643
Location:1 → 123

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_001308060.2 → NP_001294989.1 stAR-related lipid transfer protein 4 isoform d

See identical proteins and their annotated locations for NP_001294989.1

Status: VALIDATED

Description

Transcript Variant: This variant (7) lacks two internal exons, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AK026207, AK054566, AK125317, AK315863, BI091150, BU607573, DB475661

UniProtKB/TrEMBL

B0AZS2, Q86T95

Conserved Domains (1) summary

cl14643
Location:1 → 107

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_001308061.2 → NP_001294990.1 stAR-related lipid transfer protein 4 isoform c

See identical proteins and their annotated locations for NP_001294990.1

Status: VALIDATED

Description

Transcript Variant: This variant (6) lacks an internal exon, resulting in differences in the 5' UTR and translation initiation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (c) is shorter at the N-terminus, compared to isoform a. Both variants 5 and 6 encode isoform c.

Source sequence(s)

AK026207, AK054566, AK125317, BI091150, BP247836, BU607573, DB475661

UniProtKB/Swiss-Prot

Q96DR4

Conserved Domains (1) summary

cl14643
Location:1 → 123

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
NM_139164.3 → NP_631903.1 stAR-related lipid transfer protein 4 isoform a

See identical proteins and their annotated locations for NP_631903.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a). Both variants 1 and 2 encode isoform a.

Source sequence(s)

AK026207, AK054566, AK125317, BI091150, BU607573, DB475661

Consensus CDS

CCDS4104.1

UniProtKB/Swiss-Prot

Q86TN9, Q96DR4

UniProtKB/TrEMBL

A8K2P7

Related

ENSP00000296632.3, ENST00000296632.8

Conserved Domains (1) summary

cl14643
Location:5 → 205

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

RNA

NR_131752.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (8) lacks an alternate internal exon and contains alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AK308851, BC042956, DB475661
NR_131753.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (9) contains alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

BC019632, BC042956, DB475661

Related

ENST00000509887.5
NR_131754.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (10) uses an alternate splice site in the 5' terminal exon and also in an internal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AK026207, AK054566, AK125317, BI091150, BU607573

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

111496033..111512535 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017009043.3 → XP_016864532.1 stAR-related lipid transfer protein 4 isoform X3

UniProtKB/TrEMBL

B0AZS2, Q86T95

Conserved Domains (1) summary

cl14643
Location:1 → 107

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
XM_017009044.3 → XP_016864533.1 stAR-related lipid transfer protein 4 isoform X2

Conserved Domains (1) summary

cl14643
Location:1 → 123

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily
XM_047416728.1 → XP_047272684.1 stAR-related lipid transfer protein 4 isoform X3

UniProtKB/TrEMBL

B0AZS2, Q86T95
XM_024454364.2 → XP_024310132.1 stAR-related lipid transfer protein 4 isoform X1

Conserved Domains (1) summary

cl14643
Location:5 → 132

SRPBCC; START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) ligand-binding domain superfamily

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

112006333..112022835 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054351637.1 → XP_054207612.1 stAR-related lipid transfer protein 4 isoform X3

UniProtKB/TrEMBL

B0AZS2, Q86T95
XM_054351635.1 → XP_054207610.1 stAR-related lipid transfer protein 4 isoform X2
XM_054351636.1 → XP_054207611.1 stAR-related lipid transfer protein 4 isoform X3

UniProtKB/TrEMBL

B0AZS2, Q86T95
XM_054351634.1 → XP_054207609.1 stAR-related lipid transfer protein 4 isoform X1